title: Genetic variants of coagulation factor XI show association with ischemic stroke up to 70 years of age.
abstract: OBJECTIVE
  Coagulation factor XI (FXI) has an important role in the propagation and stabilization of a thrombus upon vessel injury. High FXI levels have been implicated in thrombotic diseases including ischemic stroke. The aim of our study was to investigate whether FXI gene (F11) variants are associated with ischemic stroke.
  
  
  METHODS
  The discovery sample, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), included 844 patients with ischemic stroke and 668 controls, all aged 18-70 years. Replication was performed in the Lund Stroke Register (LSR) and Malmö Diet and Cancer study (MDC), together including 1213 patients and 788 controls up to 70 years of age, and in total 3145 patients and 1793 controls (18-102 years). Seven F11 single-nucleotide polymorphisms (SNPs) were selected using a tagging approach.
  
  
  RESULTS
  The SNPs rs3733403, rs925451, and rs1593 showed independent associations with overall ischemic stroke in SAHLSIS, ORs of 0.74 (95% CI 0.59-0.94), 1.24 (95% CI 1.06-1.46), and 0.70 (95% CI 0.55-0.90), respectively. The association for rs925451 was replicated in the LSR and MDC sample in a pre-specified analysis of subjects aged 70 years or younger, OR of 1.16 (95% CI 1.00-1.34), whereas no SNP was replicated when all ages were included. In line with this, one F11 haplotype was associated with overall ischemic stroke in the discovery sample and in the replication sample ≤70 years.
  
  
  CONCLUSIONS
  We found significant associations between F11 variation and overall ischemic stroke up to 70 years of age. These findings motivate further studies on the role of F11 in ischemic stroke, especially in younger individuals.
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ellen
authors.initials: E
authors.lastname: Hanson
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Katarina
authors.initials: K
authors.lastname: Jood
authors.forename: Bo
authors.initials: B
authors.lastname: Norrving
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.forename: Christian
authors.initials: C
authors.lastname: Blomstrand
authors.forename: Arne
authors.initials: A
authors.lastname: Lindgren
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.forename: Christina
authors.initials: C
authors.lastname: Jern
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D005172:Factor XI / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020521:Stroke / Q000235:genetics*; D013548:Sweden
chemical_list: D005172:Factor XI